Although it is clear that both hypoinsulinemia and insulin resistance exist in patients with noninsulin dependent diabetes mellitus (NIDDM), the relationship between these two defects is not clear. Thus, there is evidence that either defect could be the primary abnormality in patients with NIDDM, the other being a secondary phenomenon. The studies proposed represent an effort to define this relationship in patients with NIDDM. The studies will consist of measuring in vivo insulin action in patients with NIDDM before, and after, control of their diabetes with insulin. If insulin replacement reduces the magnitude of the insulin resistance, it will suggest that insulin deficiency is the primary, and insulin resistance the secondary, defect in patients with NIDDM. Alternatively, persistence of insulin resistance in the presence of insulin replacement will suggest that the primary defect in NIDDM is loss of normal in vivo insulin action. The results of these experiments should provide useful information relevant to the pathogenesis of NIDDM.